Endocrine reviews最新文献

Vitamin D deficiency during pregnancy is associated with an increased risk of health issues in the offspring. Accordingly, recent Endocrine Society guidelines strongly support supplementation in pregnancy, also underlining that without consensus on optimal maternal vitamin D levels, routine screening is currently irrelevant. Knowledge of organ-specific effects of vitamin D and its association with maternal vitamin D status may aid in optimizing vitamin D supplementation. This systematic review outlines the proposed next-generation effects of vitamin D supplementation ≥400 IU/d and explores whether such effects are attributed to a specific maternal vitamin D level obtained during pregnancy. A systematic literature search was conducted in PubMed and Embase according to the PRISMA guidelines, focusing on health outcomes from 10 days postpartum and beyond. Of the 2383 screened articles, 38 were included. In 11 of 16 studies, vitamin D supplementation reduced respiratory tract infections in the first years of life. Growth or bone development benefits were observed in 6 of 12 studies. Positive effects on neurodevelopment and reduced autoimmune risk (diabetes-related antibodies) were noted, although further research is needed to determine the role of vitamin D. Very few studies have measured vitamin D concentrations, but even 1600 IU/d supplementation was associated with high frequency of infant vitamin D insufficiency. Current recommendations may not ensure sufficient vitamin D levels at birth, among others, increasing the risk of early-life infections. Further studies linking maternal and infant vitamin D levels to specific outcomes would aid in personalized nutritional advice during pregnancy and improve next-generation health.

The aim of this review is to describe the complex evolutionary processes that have integrated signaling cascades associated with 2 structurally and mechanistically dissimilar receptor families: G protein-coupled receptors (GPCRs) and membrane-spanning tyrosine kinase receptors (RTKs). Precision medicine, employing advanced personalized therapeutic strategies, requires better understanding of multiple mechanisms governing both normal and pathological cell regulation. The functional overlap of GPCRs and RTKs exhibits complex interactions. GPCRs canonically activate signaling through their interactions with G proteins; however, they can also initiate G protein-independent signaling through interactions with β-arrestin 1/2. In contrast to the GPCRs, RTK canonical signaling is initiated with ligand-dependent receptor kinase-mediated phosphorylation of specific intrinsic tyrosine substrates. This, in turn, activates multiple intracellular pathways. Despite these distinguishing characteristics, GPCRs and RTKs might have a common evolutionary origin. This shared ancestry potentially explains why GPCRs and RTKs can behave as functional RTK/GPCR hybrids by "borrowing" from each other's signaling toolbox. Intermingling of these cell surface receptors can result in noncanonical receptor transactivation/inactivation, trafficking, and signaling. Several mechanisms for heterogeneous receptor crosstalk have been proposed, including receptor protein/protein interactions and sharing docking, scaffolding, and downstream effectors. Recent identification of these signaling complexities has revealed unanticipated feedback loops and patterns of downstream target gene activation. In sum, recognizing these biological complexities should facilitate novel approaches to high-specificity therapeutic targeting.

Obesity is increasing rapidly worldwide and is projected to affect approximately half the US population by the year 2035. Obesity is a complex condition, and individuals who have obesity are at greater risk for developing associated metabolic diseases such as type 2 diabetes (T2D), metabolic dysfunction-associated steatohepatitis (MASH), and cardiovascular diseases (CVD). Understanding the underlying factors which contribute to obesity and that impact key molecular mechanisms of metabolic organs such as adipose tissue, liver, and muscle is crucial for combating the disease. Exercise is a well-established measure to prevent or mitigate the adverse consequences of obesity, with several beneficial effects to whole-body metabolism and adaptations to metabolic tissues. This review explores the impact of obesity on the development of metabolic diseases. Specifically, we will discuss: how obesity alters metabolic function and the potential benefits of exercise; the specific effects of obesity and exercise on muscle, adipose tissue, and liver; and potential effects of pharmacotherapeutics or bariatric surgery in combination with exercise.

Climate change is a major threat to the world's population and is due to global warming from human activities that increase atmospheric greenhouse gas levels-burning fossil fuels, industry emissions, vehicular exhaust, and aerosol chlorofluorocarbons-that trap heat in the Earth's atmosphere and adversely impact air quality. Resulting higher global temperatures, extreme weather events, and rising sea levels lead to greater frequency of wildfires and floods, which, in turn, result in population displacements and threaten air and water quality, food and water security, economic and public health infrastructures, and societal safety. Climate change has direct and indirect impacts on human health and well-being across the globe, with disproportionate impact on vulnerable populations including women, pregnant persons, the developing fetus, children, older adults, indigenous peoples, persons with disabilities, preexisting and/or chronic medical conditions, and low income and communities of color. As consequences of climate change, global mortality and noncommunicable diseases are mounting because of lack of progress to reverse current trends. Climate change effects on reproductive processes and outcomes have received less attention globally, despite huge consequences for human development, fertility, and pregnancy outcomes. This review provides evidence for direct and indirect effects of climate change on human health with a focus on reproductive processes and outcomes based on experimental models and epidemiologic data, and strategies to mitigate harms. The goal is to increase awareness about climate effects on reproductive health among clinicians, researchers, the public, and policymakers, and to engage all stakeholders to change the current trajectory of harm.

Metabolic dysfunction-associated steatotic liver disease (MASLD; previously nonalcoholic fatty liver disease) is the most common chronic liver condition globally. It affects 1 in 3 individuals and is associated with increased liver and cardiovascular mortality. MASLD is a sexually dimorphic condition, and in women the prevalence and severity of MASLD rises significantly following menopause. Preclinical data shows that lack of estrogen promotes multisystem metabolic dysfunction that is characteristic of MASLD. This not only includes hepatic lipid accumulation, insulin resistance, and fibrosis but also extra-hepatic metabolic processes in adipose and skeletal muscle. There are currently no available MASLD treatments tailored to women. The uptake of estrogen-based menopausal hormone replacement therapy (HRT) has seen a dramatic increase in recent years. Despite the changing attitudes toward HRT and the strong evidence base implicating estrogen deficiency in the development of MASLD, the impact of HRT on MASLD in postmenopausal women is poorly studied. In this review, we discuss the burden of MASLD in women, the effect of estrogen deficiency on the processes that drive MASLD development and progression, and the potential sex-specific therapeutic strategies that may prevent or limit MASLD development after menopause.